The Strategic Vision of the Southwest Environmental Health Sciences Center (SWEHSC) is to facilitate and implement innovative research aimed at understanding the mechanisms underlying the modulation of human disease risks due to environmental exposures among populations living in arid environments. The objective is to bring interdisciplinary scientists together to study the environment, genetics, and the resulting toxicology that influence morbidity in our underserved American Indian and Hispanic communities. SWEHSC incorporates state-of-the-art technologies across the environmental health sciences to assess exposures and health risks (Human Population and Exposure Resource, IHSFC) including small molecule detection and quantification (Emerging Contaminants Analytical Resource, IHSFC), subcellular confocal imaging (Cellular Imaging Facility Core), genetic and genomic/epigenomic analyses (Genomics Facility Core), and cutting-edge bioinformatics (Data Science Resource, IHSFC) in exposed communities, and through a strong Community Engagement Core program that focuses on the social and cultural needs and practices of affected people. The themes of the SWEHSC are demonstrated through three Research Focus Groups (RFG). RFG1, Environmental Exposures to Southwest Populations, works with multiple stakeholder groups to assess multiple routes of exposure in arid environments. RFG2, Environmental Lung Disease, must account for the low humidity and high wind velocities that result in complex inhalation exposures. RFG3, Adaptive Responses to Environmental Stress, focuses on the molecular pathways of adaptive responses to environmental stressors such as arsenic and ultraviolet light that result in oxidative stress. The desert Southwest is the only US region that adequately represents much of the world's arid habitats; thus, the accomplishments of the SWEHSC will have broad applicability to other diverse populations. This is essential to our long-term goal of improving the lives of the people in arid environments by developing rational approaches to mitigating their risks of hazardous environmental exposures and by developing intervention strategies to reduce adverse health outcomes.